Organozinc reagents are highly desirable reagents for organic synthesis. They possess many attributes that are distinct from other organometallic reagents. For example, they often react stereoselectively and regioselectively and do not possess the extreme nucleophilicity of such reagents as Grignard reagents. Consequently, organozinc reagents can generate distinctly different chemistry from that of other organometallic reagents, such as the synthesis of organic compounds that are highly functionalized.
Although there are several procedures known for the reduction of metal salts to metal powders reactive towards oxidative addition, each metal typically requires unique permutations of the procedures to obtain a reactive species. There is no standardized approach that can produce metal powders of identical, or even similar reactivity. For example, magnesium metal in the form of a black powder can be obtained by reducing magnesium salts in an ethereal solvent with molten sodium or potassium. However, the use of an alkaline metal in conjunction with an electron carrier such as naphthalene can produce magnesium powder of different reactivity.
Organozinc compounds are typically prepared by the oxidative addition of zinc metal to alkyl iodides. The reaction is limited, however, due to the low reactivity of the metal. Several methods have been used to activate zinc towards oxidative addition reactions. These include methods such as washing with HCl solution, using a Zn--Cu couple, ultrasound irradiation, and metal-solvent cocondensation, for example. In spite of these methods, the direct oxidative addition of zinc metal to organic halides has been limited to relatively reactive halides such as alkyl iodides or .alpha.-haloesters. Recently, zinc homoenolates of alkyl propionates were prepared by ring-opening reactions of 1-siloxy-1-alkoxycyclopropanes. However, most alkyl bromides, alkyl chlorides, vinyl halides, and aryl halides do not directly react with zinc metal.
Because of the low reactivity of metallic zinc, very little has been done to study the reactivity of organozinc halides (RZnX) or R.sub.2 Zn. The conjugate addition of alkyl halides to .alpha.,.beta.-unsaturated ketones mediated by a Zn/Cu couple in aqueous media has been reported. Furthermore, copper (I) salts have been used to mediate the 1,4-addition of organozinc species to .alpha.,.beta.-unsaturated ketones. Lithium and magnesium triorganozincates also undergo 1,4-additions with .alpha.,.beta.-unsaturated ketones. However, only one of the three organic moieties is transferred in the process. This problem has been solved to some degree by utilizing only one equivalent of the alkyllithium and two equivalents of methyl-lithium in forming these reagents. The methyl group appears to be a good, nontransferable "dummy" ligand for the lithium trialkylzincates. However, since trialkylzincate reagents are derived from the Grignard or lithium precursors, they offer no distinct advantage over the known zinc cuprate reagents, which do not have wide applicability.
The synthesis of many drugs, agrochemicals, monomers for use in polymers, highly conducting polymers, dyes, synthetics fibers, fluorocarbons, and a long list of other specialty chemicals require the use of organometallic intermediates at some stage of the synthesis. An important organometallic intermediate in various of these syntheses is an organozinc compound. Many of these organozinc compounds can only be prepared via a transmetallation reaction using Grignard reagents (organomagnesium reagents) or organolithium reagents. One of the major problems with these methods, however, is that the presence of many desirable functional groups (i.e., esters, ketones, nitriles, epoxides, .alpha.,.beta.-unsaturated ketones, etc.) in the organic portion of the compounds is precluded.
Therefore, a highly reactive zinc that would directly oxidatively add to a wide variety of carbon-halogen bonds in the presence of many or all of the above mentioned functional groups is needed. The present invention fulfills a need for such a highly reactive zinc reagent and resultant organozinc reagents having a variety of functional groups. These organozinc reagents can be utilized in further synthesis of various chemical compounds that can be useful in drugs, agrochemicals, monomers for polymers, highly conducting polymers, etc.
An object of the invention is to produce a zinc species that is more reactive than those obtained from traditional methods. Another object of the invention is to produce a zinc species that is highly reactive towards oxidative addition. Yet another object of the invention is the direct production of a wide variety of organozinc compounds, e.g., aryl, heterocyclic, arylalkyl, and polymeric zinc reagents that can undergo a number of valuable synthetic reactions. Still another object of the invention is to produce a wide variety of organozinc reagents that contain a broad spectrum of functional groups such as esters, ketones, nitrites, halides, amides, carbamates, epoxides, aldehydes, .alpha.,.beta.-unsaturated enones (e.g., esters and. ketones), sulfoxides, sulfones, etc. Furthermore, an object of the invention is the synthesis of new organic compounds or the synthesis of known organic compounds using more effective and/or more direct synthetic methods.